a feasibility study for convernsion therapy using s1/paclitaxel chemotherapy plus apatinib in elm gastric cancer

Conditions: Gastric Cancer

Summary: the prognosis of extensive lymph nodes metastatic(elm) gastric cancer is poor. chemotherapy occasionally converts it to a resectable cancer. previous studies showed patients with elm gastric cancer may obtain a survival benefit from chemotherapy and subsequent curative surgery. the key of conversion therapy of elmgc is the high response rate. apatinib, a novel targeted inhibitor of vegf receptor 2 (vegfr2), shows significant antitumor activity in the patients with gc. on the basis of our previous ahead-g325 study, the purpose of this study is to investigate the efficacy and safety of s1/paclitaxel chemotherapy plus apatinib in the conversion therapys of elm gastric cancer.

the investigators will apply spa regimen for coversional therapy to abtain high response rate. paclitaxel：150 mg/m2 i.v.3h , given on the first day. apatinib, oral ,initial dose :425mg, qd, after meal ( try to take the medicine at the same time of the day ). dose adjustment: down-regulate the dosage to 250 mg per day at the first time. if the patient totally recovers from the toxic reaction after the regulation, we could up-regulate the dosage back to the former level. if the downregulation occurs again according to the protocol , then the up-regulation will be forbidden. s-1 dosage: according to the body surface area, the initial dosage of s-1 is decided by the following criteria. take the medicine twice daily (after breakfast and supper) for 2 weeks, then suspend for 1 week. preventive medication: to prevent serious allergic reaction of paclitaxel, preventive medication should be given in advance. we usually give dexamethasone 20mg orally 12 and 6 hours before the paclitaxel, and diphenhydramine (or something analogous) 50 mg, cimetidine 300mg (or ranitidine 50mg) i.v. 30-60 minutes before the paclitaxel. repeat the therapeutic schedule every 3 weeks. 3-4 cycles of neoadjuvant chemotherapy before surgery, stop apatinib in the last cycle.4 cycles of adjuvant chemotherapy including s-1 and apatinib 4 to 6 weeks after surgery.

Eligibility criteria:
inclusion criteria: * elm gastric cancer as proven histologically under following condition: unable radical excision due to the abdominal aorta a2-b1 or extensive lymph nodes metastatic, * definitely diagnosed as above stage of gastric cancer before operation via ct of mri, ultrasonic endoscopy, pet-ct, or through the laparoscopic exploration if necessary * untreated (e.g. radiotherapy, chemotherapy, target therapy and immunotherapy) * negative her-2 state * ecog(eastern cooperative oncology group): 0\~2 * age: 18\~70 years old- survival time \> 3monts * normal hemodynamic indices before the recruitment(including blood cell count and liver/kidney function ). for example: wbc\>4.0\*109/ l, ne\>1.5\*109/l, plt\>100\*109/l, bil\<1.5 times of upper limit of normal reference value, alt and ast\<2.5 times of upper limit of normal reference value, and cre\<1.2mg/dl * good cardiac function before the recruitment, no seizure of myocardial infarction in past half years, and controllable hypertension and other coronary heart disease * not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver) * not participating in other clinical trials before and during the treatment * signed the informed consent form * no peritoneal metastatic and cy0 in 28 days by laparoscopic exploration * non-gastric stump cancer * no esophagus infiltrating or infiltrating less than 3cm exclusion criteria: * distal metastasis to mediastinal lymph node,liver ,peritoneal,pleural effusion ,ascites,above 16a2-b1 and others * severe mental illness * her-2 positive, desire for hercptin treatment * ever administrated with other drugs(including tcm drugs) before the recruitment, or no guarantee of progress according to the study requirement after recruitment * allergy to the drugs in this protocol * pregnant and lactating women * women at childbearing age and of pregnancy desire during the study

Keywords: conversion therapy